title: Hippocampus-related cognitive impairments in young apoE4 targeted replacement mice.
abstract: We presently investigated the effects of apolipoprotein E4 (apoE4), the most prevalent genetic risk factor for Alzheimer's disease, on the cognitive performance of young targeted replacement apoE4 mice. We revealed that these mice were impaired in the object recognition and Morris water maze tests, both of which are associated with hippocampal learning and memory, relative to that of the apoE3 mice. These results are consistent with previous histological and biochemical findings that hippocampal neurons are specifically affected by apoE4. The suggestion that the behavioral impairments of the apoE4 mice are related to the hippocampal neuropathology of these mice is further supported by the fear conditioning test. This test revealed that the performance of the apoE4 mice in the contextual component, which is hippocampus related, was impaired, whereas their cued test response, which is amygdala driven, was not. The stress levels of the apoE4 and apoE3 mice, as unraveled by the light/dark anxiety test, were similar, suggesting that the observed cognitive impairments of the apoE4 mice are not related to differences in the basal anxiety levels of these mice. In conclusion, the present study shows that young apoE4 targeted replacement mice are impaired in numerous hippocampus-related learning and memory tasks.
authors.affiliation: Department of Neurobiology, George S. Wise Faculty of Life Sciences, Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Shiran
authors.initials: S
authors.lastname: Salomon-Zimri
authors.forename: Anat
authors.initials: A
authors.lastname: Boehm-Cagan
authors.forename: Ori
authors.initials: O
authors.lastname: Liraz
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Michaelson
mesh_terms: D000375:Aging; D000544:Alzheimer Disease / Q000235:genetics* / Q000503:physiopathology; D000818:Animals; D053327:Apolipoprotein E4 / Q000235:genetics*; D003072:Cognition Disorders / Q000235:genetics / Q000503:physiopathology*; D004195:Disease Models, Animal; D006624:Hippocampus / Q000503:physiopathology*; D006801:Humans; D007858:Learning / Q000502:physiology; D008568:Memory / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D053327:Apolipoprotein E4